EVALUATION OF PLASMA M2 PYRUVATE KINASE IN BREAST CANCER

Abstract

Cancer stands as one of the most heterogeneous human diseases. It can be caused by many factors-most of which are still unknown or only partially understood.

Glycolysis is the sequence of reactions that converts glucose into pyruvate with the concomitant production of relatively small amount of adenosine triphosphate (ATP). PK is a rate controlling glycolytic enzyme which catalyses the formation of pyruvate and ATP from phosphoenol pyruvate (PEP) and ADP. PK esists as hour isoenzymes which are referred to the L,R,M, and M2- type. The expression of the PK isoenzymes is developmental regulated. The M2- PK is only detectable isoenzyme in early fetal tissues and during development it is gradually replaced by the L, R, or M1 isoenzyme.All PKs are cytosolic enzymes and function as tetramer. Pyruvate kinase is the most enegy rich cellular phosphometabolite. During tumerogensis the tissue specific isoenzyme generally disappears and M2-PK is expressed in tumor cells generally the dimeric form of M2-PK is dominat and released into the blood. Therefore, the dimeric form of M2-PK was known as Tumor M2-PK (Tu M2-PK). This dissociation from tetrameric form to dimeric form occurs by oncoprotein (HPV-16E7 and PP60v-src). TuM2-PK found to be a good marker for solid tumor (GI, lung, colorectal & Breast).

Cancer antigen 15.3 (CA15.3) is elevated in a proportion of breast cancer patient with distant metastases. CA 15.3 is a useful marker in monitoring the clinical course of patients after definitive surgery.

The aim of this study was to evaluate plasma M2-PK as a diagnostic marker in metastasized breast cancers in combination with the well known CA15.3 as a routine tumor marker. The additive value of the two markers (M2-PK and CA15.3) in diagnosing the increasing burden of breast cancer metastasis was also investigated. Seventy women were randomly selected from patients referred to the clinic of the oncology department, Medical Research Institute, Alexandria University. All patient samples are quantified to TuM2-PK and CA15.3. TuM2-PK showed increased level in metastatic and non- metastatic patient when compared to the control patient.

No significant difference was observed with LM or LN number or ER or PR or grade or stage or menopausal status except significantly increased with tumor size (p = 0.007). CA15.3 elevated in metastatic patient 63.6% but only 12% in non-metastatic patient. Positive correlation between TuM2-PK and CA15.3 was observed. The survival rate increased significantly in patients with TuM2- PK level less than 15 U/ml in non metastatic group. No significant differences were observed between survival rates or free all survival and TuM2-PK level in non metastatic group. TuM2-PK showed high diagnostic performance higher than CA15.3 in non metastatic group but in the other hand CA15.3 showed higher diagnostic performance than TuM2-PK in metastatic group.